title: Incretin actions beyond the pancreas: lessons from knockout mice.
abstract: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are intestinal hormones secreted in response to ingestion of various nutrients. These incretins stimulate insulin secretion from pancreatic β cells in a glucose-dependent fashion. GIP and GLP-1 actions are mediated by specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which are expressed in pancreatic β cells and various other tissues and organs. Investigations using mice deficient in GIPR and/or GLP-1R have clarified roles of the incretins in enhancement of glucose-dependent insulin secretion from βcells as well as divergent biological activities with therapeutic implications for diabetes-related complications, such as cardiovascular diseases, retinopathy, nephropathy and neuropathy, and comorbidities, such as cognitive impairment, bone fracture and obesity. We review here recent findings on the extra-pancreatic effects of GIP and GLP-1 from the perspective of diabetes treatment.
authors.affiliation: Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan; Division of Metabolism and Clinical Nutrition, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
mesh_terms: D000818:Animals; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D054795:Incretins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1